Colorectal cancer

Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as  microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC).

Cancer

beta-Catenin (mutation) [HSA:1499] [KO:K02105]
K-ras (mutation) [HSA:3845] [KO:K07827]
APC (germline mutation (FAP), somatic mutation) [HSA:10297] [KO:K02085]
DCC (deletion) [HSA:1630] [KO:K06765]
TGF-betaRII (mutation) [HSA:7048] [KO:K04388]
Smad2 (mutation) [HSA:4087] [KO:K04500]
Smad4 (deletion) [HSA:4089] [KO:K04501]
BAX (mutation) [HSA:581] [KO:K02159]
p53 (deletion) [HSA:7157] [KO:K04451]
MLH1 (germline mutation (HNPCC), LOH, promoter hypermethylation) [HSA:4292] [KO:K08734]
MSH2 (germline mutation (HNPCC), LOH, somatic mutation) [HSA:4436] [KO:K08735]
MSH3 (somatic frameshift mutation) [HSA:4437] [KO:K08736]
MSH6 (germline mutation (HNPCC), LOH, somatic frameshift mutation) [HSA:2956] [KO:K08737]

Mineral oils, untreated and mildly treated
X- and gamma-radiation

Hemoglobin [HSA:3039 3040 3043]
K-ras (mutation) [HSA:3845]
p53 (mutation) [HSA:7157]
APC (mutation) [HSA:10297]
BAT-26 (mutation)

Oxaliplatin [DR:D01790]
5-Fluorouracil (5-FU) [DR:D00584]
Leucovorin (FOLFOX4) [DR:D01211 D04715]
Bevacizumab [DR:D06409]
Irrinotecan [DR:D01061]
Cetuximab [DR:D03455]
Capecitabine [DR:D01223]

ICD-O: 8140/3, Tumor type: Adenocarcinoma

PMID:15000146 (gene, tumor type)

Grady WM.

Genomic instability and colon cancer.

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PMID:11477132 (tumor type)

Houlston RS.

What we could do now: molecular pathology of colorectal cancer.

Mol Pathol 54:206-14 (2001)

PMID:16555243 (gene)

Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.

Microsatellite instability in colorectal cancer.

Br J Surg 93:395-406 (2006)

PMID:12621137 (gene)

Lynch HT, de la Chapelle A.

Hereditary colorectal cancer.

N Engl J Med 348:919-32 (2003)

PMID:15310786 (gene)

Mehlen P, Fearon ER.

Role of the dependence receptor DCC in colorectal cancer pathogenesis.

J Clin Oncol 22:3420-8 (2004)

PMID:9498901 (carcinogen)

Tolbert PE.

Oils and cancer.

Cancer Causes Control 8:386-405 (1997)

PMID:15070562 (carcinogen)

Berrington de Gonzalez A, Darby S.

Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.

Lancet 363:345-51 (2004)

PMID:15929776 (marker)

Ouyang DL, Chen JJ, Getzenberg RH, Schoen RE.

Noninvasive testing for colorectal cancer: a review.

Am J Gastroenterol 100:1393-403 (2005)

PMID:15738983 (marker)

Davies RJ, Miller R, Coleman N.

Colorectal cancer screening: prospects for molecular stool analysis.

Nat Rev Cancer 5:199-209 (2005)

(drug)

McPhee SJ, Papadakis MA, Tierney LM (ed).

Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition

The McGraw-Hill Companies, Inc. (2007)